Interest in the percutaneous or transdermal delivery of peptides and proteins to the human body continues to grow as the number of medically useful peptides and proteins becoming increasingly available in large quantities and pure form. The transdermal delivery of peptides and proteins still faces significant problems. In many instances, the rate of delivery or flux of polypeptides through the skin is insufficient, due to their large size and molecular weight, to produce a desired therapeutic effect. In addition, polypeptides and proteins are easily degraded during and after penetration into the skin and prior to reaching target cells. Likewise, the passive transdermal flux of many low molecular weight compounds is too low to be therapeutically effective.
One method of increasing the transdermal delivery of agents relies on utilizing a skin permeation enhancer, either by pretreatment of the skin or co-delivering it with the beneficial agent. A permeation enhancer substance, when applied to a body surface through which the agent is delivered, enhances the transdermal flux of the agent. These enhancers work may function increasing the permselectivity and/or permeability of the body surface, and/or reducing the degradation of the agent.
Another method of increasing the agent flux involves the application of an electric current across the body surface referred to as “electrotransport.” “Electrotransport” refers generally to the passage of a beneficial agent, e.g., a drug or drug precursor, through a body surface, such as skin, mucous membranes, nails, and the like. The transport of the agent is induced or enhanced by the application of an electrical potential, which results in the flow of electric current, which delivers or enhances delivery of the agent. Electrotransport delivery generally increases agent delivery and reduces polypeptide degradation during transdermal delivery.
There also have been many attempts to mechanically penetrate or disrupt the skin in order to enhance the transdermal flux, such as, U.S. Pat. No. 5,879,326 issued to Godshall, et al., U.S. Pat. No. 3,814,097 issued to Ganderton, et al., U.S. Pat. No. 5,279,544 issued to Gross, et al., U.S. Pat. No. 5,250,023 issued to Lee, et al., U.S. Pat. No. 3,964,482 issued to Gerstel, et al., Reissue 25,637 issued to Kravitz, et al., and PCT Publication Nos. WO 96/37155, WO 96/37256, WO 96/17648, WO 97/03718, WO 98/11937, WO 98/00193, WO 97/48440, WO 97/48441, WO 97/48442, WO 98/00193, WO 99/64580, WO 98/28037, WO 98/29298, and WO 98/29365. These devices use piercing elements of various shapes and sizes to pierce the outermost layer (i.e., the stratum corneum) of the skin. The penetrating elements disclosed in these references generally extend perpendicularly from a thin, flat member, such as a pad or sheet. The penetrating elements, often referred to as microblades, are extremely small in some devices. Some of these microblades have dimensions (i.e., a microblade length and width) of only about 25-400 μm and a microblade thickness of only about 5-50 μm. Other penetrating elements are hollow needles having diameters of about 10 μm or less and lengths of about 50-100 μm. These tiny stratum corneum piercing/cutting elements are meant to make correspondingly small microslits/microcuts in the stratum corneum for enhanced transdermal agent delivery, or for enhanced transdermal efflux of a body analyte, therethrough. The perforated skin provides improved flux for sustained agent delivery or sampling through the skin. In many instances, the microslits/microcuts in the stratum corneum have a length of less than 150 μm and a width which is substantially smaller than their length.
When microprotrusion arrays are used to improve delivery or sampling of agents through the skin, consistent, complete, and repeatable penetration of the skin by the microprotrusions is desired. Manual application of a skin patch including microprotrusions often results in significant variation in puncture depth across the microprotrusion array. In addition, manual application results in large variations in puncture depth between applications due to the manner in which the user applies the array. Accordingly, it would be desirable to be able to apply a microprotrusion array to the stratum corneum with an automatic or semi-automatic device which provides microprotrusion skin penetration in a consistent and repeatable manner.
It would be desirable to provide an applicator for consistent and repeatable application of a microprotrusion array to the skin with the applicator applying an impact capable of achieving effective penetration of the stratum corneum with the microprotrusion array.